罗程,张元斌,应俊,徐涛涛,王萍儿,金红婷,童培建,肖鲁伟

• 1:浙江中医药大学第一临床医学院
• 2:浙江省骨伤研究所
• 3:浙江中医药大学第一附属医院

摘要(Abstract)：

<正>血管内皮生长因子(VEGF),又称血管渗透因子(VPF),是一个以二硫键或非共价键联接的同源二聚体糖蛋白,是机体最主要的血管生成因子。根据编码VEGF m RNA的剪接方式不同,VEGF蛋白含氨基酸数目具有5种形式:VEGF121、VEGF165、VEGF189、VEGF206和VEGF145,以VEGF165较为常见[1]。股骨头坏死(ONFH)是一种由多种原因引起股骨头内活性

关键词(KeyWords)： 股骨头坏死;血管内皮生长因子;信号通路;综述

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金资助项目(81273770);国家自然科学基金资助项目(81373669);; 浙江省科技厅重大专项(2012C13017-2);; 浙江省中西医结合骨关节病研究科技创新团队(2011R50022);; 浙江省骨关节疾病中医药干预技术研究重点实验室(2013E10024)

作者(Author): 罗程,张元斌,应俊,徐涛涛,王萍儿,金红婷,童培建,肖鲁伟

参考文献(References)：

• [1]Ferrara N.Binding to the extracellular matrix and proteolytic processing:two key mechanisms regulating vascular endothelial growth factor action[J].Mol Biol Cell,2010,21(5):687-690.
• [2]T.H.Kim Ph.D.yx,J.M.Hong M.Sc.y,et al.Promoter polymorphisms of the vascular endothelial growth factor gene is associated with an osteonecrosis of the femoral head in the Korean population[J].Osteoarthritis and Cartilage,2008,16(3),287-291.
• [3]Li W,Sakai T,Nishii T,et al.Distribution of TRAP-positive cells and expression of HIF-1alpha,VEGF,and FGF-2 in the reparative reaction in patients with osteonecrosis of the femoral head[J].Orthop Res,2009,27(5):694-700.
• [4]Proliferative and secretory activity of human umbilical vein endothelial cells cultured under varying degrees of hypoxia[J].Tsitologiia,2014,56(1):67-76.
• [5]Yang Z1,Wang C2.Endothelial progenitor cells induce transplant arteriosclerosis via VEGFR-1/2 activity[J].Atherosclerosis,2014,238(1):26-32.
• [6]Lee IS,Kim YS,Jung SH,et al.Lignans from the stems and leaves of Brandisia hancei and their effects on VEGF-induced vascular permeability and migration of HRECs and DLAV formation in zebrafish[J].Bioscience,Biotechnology and Biochemistry,2014,15(12):1-6.
• [7]章静茹.Notch/D114和VEGF信号通路在急性髄性白血病血管新生中的交互作用及机制研究[D].济南:山东大学,2013.
• [8]王苹苹,孔繁平,陈学群,等.低氧细胞应激的HIF-1信号通路[J].浙江大学学报:医学版,2011,54(5):559-566.
• [9]Semenza GL,Rue EA,Iyer NV,et al.Assignment of the hypoxia-inducible factor 1alpha gene to a region of conserved syntenyon mouse chromosome 12 and human chromosome14q[J].Genomics,1996,34.
• [10]Forsythe JA,Jiang BH,Iyer NV,et al.Mol Cell Biol,1996,16(9):4604-4613.
• [11]Holmes K,Roberts OL,Thomas AM,et al.Vascular endothelial growth factor receptor-2:Structure,function,intracellular signalling and therapeutic inhibition[J].Cellular Signalling,2007,19(10):2003-2012.
• [12]Liu Y,Olsen BR.Distinct VEGF functions during bone development and homeostasis[J].Archivum Immunologiae et Therapiae Experimentalis,2014,62(5):363-368.
• [13]Prasadam I,Zhou Y,Du Z,et al.Osteocyte-induced angiogenesis via VEGF-MAPK-dependent pathways in endothelial cells[J].Molecular and Cellular Biochemistry,2014,386(1-2):15-25.
• [14]Lamalice L,Houle F,Jourdan G,et al.Phosphorylation of tyrosine 1214 on VEGFR2 is required for VEGF-induced activation of Cdc42 upstream of SAPK2/p38[J].Oncogene,2004,23(2):434-445.
• [15]Lamalice L,Houle F,Huot J.Phosphorylation of Tyr1214within VEGFR-2 triggers the recruitment of Nck and activation of Fyn leading to SAPK2/p38 activation and endothelial cell migration in response to VEGF[J].Biol Chem,2006,281(45):34009-34020.
• [16]康从民,王大伟,吕英涛,等.血管内皮生长因子受体-2所介导信号通路的研究进展[J].生物化学与生物物理进展,2009,36(10).
• [17]Holmqvist K,Cross MJ,Rolny C,et al.The adaptor protein shb binds to tyrosine 1175 in vascular endothelial growth factor(VEGF)receptor-2 and regulates VEGF-dependent cellular migration[J].Biol Chem,2004,279(21):22267-22275.
• [18]Olsson A,Dimberg A,Kreuger J,et al.VEGF receptor signaling-in control of vascular function[J].Nature Reviews Molecular Cell Biology,2006,7(5):359-371.
• [19]Laramée M,Chabot C,Cloutier M,et al.The scaffolding adapter Gab1 mediates vascular endothelial growth factor signaling and isrequired for endothelial cell migration and capillary formation[J].Biol Chem,2007,282(11):7758-7769.
• [20]Kaplan N,Urao N,Furuta E,et al.Localized cysteine sulfenic acid formation by vascular endothelial growth factor:role in endothelial cell migration and angiogenesis[J].Free Radical Research,2011,45(10):1124-1135.
• [21]Takahashi T,Ueno H,Shibuya M.VEGF activates protein kinase C-dependent,but Ras-independent Raf-MEK-MAP kinase pathway for DNA synthesis in primary endothelial cells[J].Oncogene,1999,18(13):2221-2230.
• [22]Downward J.PI3-kinase,Akt and cell survival[J].Semin Cell Dev Biol,2004,15(2):177-182.
• [23]Soldi R,Mitola S,Strasly M,et al.Role ofαvβ3 integrin in the activation of vascular endothelial growth factor receptor-2[J].EMBO,1999,18(4):882-892.
• [24]Yang Q,Mc Hugh KP,Patntirapong S,et al.VEGF enhancement of osteoclast survival and bone resorption involves VEGF receptor-2 signaling and beta3-integrin[J].Matrix Biol,2008,27(9):589-599.
• [25]Engsig MT,Chen QJ,Vu TH,et al.Matrix metalloproteinase 9and vascular endothelial growth factor are essential for osteoclast recruitment into developing long bones[J].Cell Biol,151(11):879-889.
• [26]Dewerchin M,Carmeliet P.Pl GF:a multitasking cytokine with disease-restricted activity[J].Cold Spring Harb Perspect Med,2012,121(9):2.
• [27]Javerzat S,Auguste P,Bikfalvi A.The role of fibroblast growth factors in vascular development[J].Trends Mol Med,2002,21(8):483-489.
• [28]Stegen S,van Gastel N,Carmeliet G.Bringing new life to damaged bone:The importance of angiogenesis in bone repair and regeneration[J].Bone,2015,70(8):19-27.
• [29]Bouletreau PJ,Warren SM,Spector JA,et al.Hypoxia and VEGF up-regulate BMP-2m RNA and protein expression in microvascular endothelial cells:implications for fracture healing[J].Plast Reconstr Surg,2002,109(7):2384-2397.
• [30]Street J,Bao M,de Guzman L,et al.Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover[J].Proc Natl Acad Sci,2002,99(12):9656-9661.
• [31]Zhang C,Wang KZ.Angiopoiesis and bone regeneration via co-expression of the h VEGF and h BMP genes from an adenoassociated viral vector in vitro and in vivo[J].Acta Pharmacol Sin,2010,31(7),821-830.
• [32]Dafu Chen,Wei Tian,Yang Li,et al.Osteoblast-specific transcription factor Osterix(Osx)and HIF-1αcooperatively regulate gene expression of vascular endothelial growth factor(VEGF)[J].Osteoarthritis and Cartilage,2008,16(12):287-291.
• [33]Ryuto M,Ono M,Izumi H,et al.[J].Biol Chem,1996,271:28220-28228.
• [34]Finkenzeller G,Sparacio A,Technau A,et al.[J].Oncogene,1997,15(1):669-676.
• [35]Tanaka S,Takahashi N,Udagawa N,et al.Macrophage colonystimulating factor is indispensable for both proliferation and differentiation of osteoclast progenitors[J].Clin Invest,1993,91(4):257-263.
• [36]Kodama H,Yamasaki A,Nose M,et al.Congenital osteoclast deficiency in osteopetrotic(op/op)mice is cured by injections of macrophage colony-stimulating factor[J].Exp Med,1991,173(12):269-272.
• [37]Niida S,Kaku M,Amano H,et al.Vascular endothelial growth factor can substitute for macrophage colony-stimulating factor in the support of osteoclastic bone resorption[J].Exp Med,1999,190(21):293-298.
• [38]Liu Y,Berendsen AD,Jia S,et al.Intracellular VEGF regulates the balance between osteoblast and adipocyte differentiation[J].Clin Invest,2012,122(12):3101-3113.
• [39]高冬,陈文元,林薇.血府逐疲汤促血管新生中VEGF通路的作用研究[J].中国中药杂志,2012,37(17):2622-2625.
• [40]李引刚,武辉,刘艳平,等.复元活血汤对早期实验性骨折愈合中VEGF、BMP-2表达的影响[J].陕西中医,2009,30(6):754-755.
• [41]高云,董福慧,郑军.海螵蛸对骨愈合相关基因表达的影响[J].中医正骨,2004,16(7):1-3.
• [42]毕锴.中医骨折分期治疗对骨折愈合b FGF、TGF-0、VEGF、BMP-2基因表达影响的实验研究[D].北京:中国中医科学院望京医院,2013.